Disruption of the blood-testis barrier integrity by bisphenol A in vitro: Is this a suitable model for studying blood-testis barrier dynamics?

Li, Michelle W.M.; Mruk, Dolores D.; Lee, Will M.; Cheng, C. Yan

doi:10.1016/j.biocel.2009.05.016

Cited by 185 publications

(184 citation statements)

References 53 publications

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“…It may also be mentionable in this context that it was reported in different studies that BTB components may act as early targets of environmental and reproductive toxicants mostly leading to testicular disorders (Defamie et al 2001, Sobarzo et al 2006, 2009, Li et al 2009a, Salian et al 2009, Pointis et al 2011.…”

Section: Sc Btb and Junctional Proteinsmentioning

confidence: 92%

Blood–testis barrier and Sertoli cell function: lessons from SCCx43KO mice

Gerber¹,

Heinrich²,

Brehm³

2016

Reproduction

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The gap junction protein connexin43 (CX43) plays a vital role in mammalian spermatogenesis by allowing for direct cytoplasmic communication between neighbouring testicular cells. In addition, different publications suggest that CX43 in Sertoli cells (SC) might be important for blood-testis barrier (BTB) formation and BTB homeostasis. Thus, through the use of the Cre-LoxP recombination system, a transgenic mouse line was developed in which only SC are deficient of the gap junction protein, alpha 1 (Gja1) gene. Gja1 codes for the protein CX43. This transgenic mouse line has been commonly defined as the SC specific CX43 knockout (SCCx43KO) mouse line. Within the seminiferous tubule, SC aid in spermatogenesis by nurturing germ cells and help them to proliferate and mature. Owing to the absence of CX43 within the SC, homozygous KO mice are infertile, have reduced testis size, and mainly exhibit spermatogenesis arrest at the level of spermatogonia, seminiferous tubules containing only SC (SC-only syndrome) and intratubular SC-clusters. Although the SC specific KO of CX43 does not seem to have an adverse effect on BTB integrity, CX43 influences BTB composition as the expression pattern of different BTB proteins (like OCCLUDIN, b-CATENIN, N-CADHERIN, and CLAUDIN11) is altered in mutant males. The supposed roles of CX43 in dynamic BTB regulation, BTB assembly and/or disassembly and its possible interaction with other junctional proteins composing this unique barrier are discussed. Data collectively indicate that CX43 might represent an important regulator of dynamic BTB formation, composition and function.Reproduction (2016) 151 R15-R27

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Section: Sc Btb and Junctional Proteinsmentioning

confidence: 92%

Blood–testis barrier and Sertoli cell function: lessons from SCCx43KO mice

Gerber¹,

Heinrich²,

Brehm³

2016

Reproduction

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“…Sertoli cells were incubated in 200 μM BPA for 24 h to induce junction disruption (9). In the vehicle control group, cells were treated with 0.1% ethanol.…”

Section: Methodsmentioning

confidence: 99%

“…However, it is unknown if Cx43 is involved in regulating the homeostasis of BTB, such as junction restructuring during the transit of preleptotene spermatocytes across the immunological barrier. In the present study, we examined the involvement of Cx43 in the reassembly of the Sertoli cell TJ barrier by using two different models, namely the calcium switch model (8) and the bisphenol A (BPA) model (9). These findings report the critical role of Cx43-based GJ in the homeostasis of the BTB during spermatogenesis.…”

mentioning

confidence: 95%

Connexin 43 is critical to maintain the homeostasis of the blood–testis barrier via its effects on tight junction reassembly

Mruk²,

Lee³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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146

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In mammalian testes, the blood-testis barrier (BTB) or Sertoli cell barrier created by specialized junctions between Sertoli cells near the basement membrane confers an immunological barrier by sequestering the events of meiotic division and postmeiotic germ cell development from the systemic circulation. The BTB is constituted by coexisting tight junctions (TJs), basal ectoplasmic specializations, desmosomes, and gap junctions. Despite being one of the tightest blood-tissue barriers, the BTB has to restructure cyclically during spermatogenesis. A recent study showed that gap junction protein connexin 43 (Cx43) and desmosome protein plakophilin-2 are working synergistically to modulate the BTB integrity by regulating the distribution of TJ-associated proteins at the Sertoli-Sertoli cell interface. However, the precise role of Cx43 in regulating the cyclical restructuring of junctions remains obscure. In this report, the calcium switch and the bisphenol A (BPA) models were used to induce junction restructuring in primary cultures of Sertoli cells isolated from rat testes that formed a TJ-permeability barrier that mimicked the BTB in vivo. The removal of calcium by EGTA perturbed the Sertoli cell tight junction barrier, but calcium repletion allowed the "resealing" of the disrupted barrier. However, a knockdown of Cx43 in Sertoli cells by RNAi significantly reduced the kinetics of TJ-barrier resealing. These observations were confirmed using the bisphenol A model in which the knockdown of Cx43 by RNAi also perturbed the TJ-barrier reassembly following BPA removal. In summary, Cx43 is crucial for TJ reassembly at the BTB during its cyclic restructuring throughout the seminiferous epithelial cycle of spermatogenesis.bisphenol A | calcium switch | gap junction | seminiferous epithelial cycle | spermatogenesis I n mammalian testes, the blood-testis barrier (BTB) segregates the epithelium of seminiferous tubules into apical and basal compartments (1, 2). Unlike other blood-tissue barriers (e.g., blood-brain barrier, blood-retina barrier) that are constituted by tight junctions (TJs) between endothelial cells of the microvessels at the apical region, the BTB is created by adjacent Sertoli cells in the seminiferous epithelium near the basement membrane. The BTB is constituted by coexisting TJs, basal ectoplasmic specialization (basal ES, a testis-specific adherens junction type), desmosome-like junction (or desmosome-gap junction), and gap junction (GJ) (1-3). Whereas the BTB is one of the tightest blood-tissue barriers, it undergoes cyclical restructuring to accommodate the transit of preleptotene spermatocytes from the basal to the apical compartment during spermatogenesis, so that meiotic divisions and postmeiotic germ cell development (i.e., spermiogenesis) can take place in the apical compartment of the seminiferous epithelium behind this immunological barrier. The immunological barrier conferred by the BTB cannot be compromised, even transiently, during the transit of preleptotene spermatocytes to avoid the product...

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“…[67][68][69] Thus, the localized production of cytokines within the microenvironment of the BTB can regulate the level of drebrin E to fine tune the homeostasis of actin filament 6 cells/cm 2 for 4 d to allow the formation of a functional tJ-permeability barrier with ultrastructural features corresponding to tJs, basal eS, GJs and desmosomes when examined by electron microscopy. 41,42,76 thereafter, lysates were obtained by using Ip lysis buffer and about 250 μg protein from each sample was used for Co-Ip. the column on the left is positive control using Sertoli cell lysates (25 μg protein) per lane alone without Co-Ip.…”

confidence: 99%

“…75 Sertoli cell purity in these cultures was >98% with negligible contamination of germ (e.g., spermatogonia and spermatocytes), peritubular myoid and Leydig cells, as earlier characterized by RT-PCR and immunoblotting using specific primer pairs or antibodies against corresponding marker genes/proteins and electron microscopy. 41,42,76 It should be noted that by ~day 2-3 these cells formed an intact epithelium and established a functional Sertoli cell TJ-permeability barrier when quantified by transepithelial electrical resistance (TER) across the cell epithelium. Ultrastructural characteristics typical of TJs, basal ES, desmosomes and GJs were also noted when Sertoli cells were examined by electron microscopy, mimicking the Sertoli cell BTB in vivo.…”

confidence: 99%